Background: Sexually transmitted infections (STIs) constitute major public health concern and enigma. A comprehensive knowledge of the modes of transmission is necessary to evolve an effective preventive strategy. Aim: The aim of the study is to assess the vulnerability, knowledge and prevention of STIs among female traders of reproductive age in Enugu, Southeast Nigeria. Subjects and Methods: This was a cross‑sectional descriptive study carried out on female traders aged 15‑49 years at Ogbete Main Market, Enugu, Southeast Nigeria. Data was analyzed using Epi‑Info 2000 version 3.3.1 Centers for Disease Control and Prevention Atlanta USA) was used to analyze the data and results were presented in tabular form. Results: A total of 200 female traders of reproductive age participated in the study. The mean (standard deviation) age was 26 (7.4) years. 16% (32/200) were adolescents. Knowledge of specific STIs was highest for human immunodeficiency virus/acquired immune deficiency syndrome 90% (130/200). Parents were poor sources of information as only 28.5% (57/200) respondents heard about STIs from their parents compared with 46% (92/200) from friends and peers. Risk factors identified were multiple sexual partners 75.5% (151/200), non‑use of condoms 62% (124/200) and early debut 58% (116/200). Majority 67.5% (135/200) were aware that STIs could be treated by a visit to the doctor while 21.5% (43/200) preferred traditional/herbal healers. Conclusion: The inclusion of health education in schools’ curricula to ensure that adolescents are adequately aware of STIs, their modes of transmission, prevention and treatment before embarking on any vocation out‑of‑school is advocated.